Drugs Details

Drugs Info of Onglyza
Drugs Details
  • Drugs Type  : Multum
  • Date : 28th Mar 2015 04:24 am
  • Brand Name : Onglyza
  • Generic Name : saxagliptin (Pronunciation: SAX a GLIP tin)
Descriptions

Saxagliptin is an orally-active inhibitor of the DPP4 enzyme.

Saxagliptin monohydrate is described chemically as (1S,3S,5S)-2-[(2S)-2-Amino-2-(3- hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, monohydrate or (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2- azabicyclo[3.1.0]hexane-3-carbonitrile hydrate. The empirical formula is C18H25N3O2•H2O and the molecular weight is 333.43. The structural formula is:

 

ONGLYZA (saxagliptin) Structural Formula Illustration

 

Saxagliptin monohydrate is a white to light yellow or light brown, non-hygroscopic, crystalline powder. It is sparingly soluble in water at 24°C ± 3°C, slightly soluble in ethyl acetate, and soluble in methanol, ethanol, isopropyl alcohol, acetonitrile, acetone, and polyethylene glycol 400 (PEG 400).

Each film-coated tablet of ONGLYZA for oral use contains either 2.79 mg saxagliptin hydrochloride (anhydrous) equivalent to 2.5 mg saxagliptin or 5.58 mg saxagliptin hydrochloride (anhydrous) equivalent to 5 mg saxagliptin and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, and iron oxides.

 

What are the possible side effects of saxagliptin (Onglyza)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
  • pain or burning when you urinate;
  • swelling in your hands, ankles, or feet; or
  • easy bruising or bleeding.

Less serious side effects may include:

  • runny or stuffy nose, sore throat, cough;
  • headache;...

Read All Potential Side Effects and See Pictures of Onglyza »

What are the precautions when taking saxagliptin tablets (Onglyza)?

Before taking saxagliptin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, disease of the pancreas (pancreatitis), risk factors for pancreatitis (such as stones in your gallbladder, regular use/abuse of alcohol, high levels of fats/triglycerides in the blood).

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you...

Read All Potential Precautions of Onglyza »

 

This monograph has been modified to include the generic and brand name in many instances.

Indications

Monotherapy and Combination Therapy

ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. [See Clinical Studies.]

Limitations of Use

ONGLYZA should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

ONGLYZA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using ONGLYZA. [SeeWARNINGS AND PRECAUTIONS]

Dosage Administration

Recommended Dosage

The recommended dosage of ONGLYZA is 2.5 mg or 5 mg once daily taken regardless of meals. ONGLYZA tablets must not be split or cut.

Dosage in Patients with Renal Impairment

No dosage adjustment for ONGLYZA is recommended for patients with mild renal impairment (creatinine clearance [CrCl] > 50 mL/min).

The dosage of ONGLYZA is 2.5 mg once daily (regardless of meals) for patients with moderate or severe renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis (creatinine clearance [CrCl] ≤ 50 mL/min) [see CLINICAL PHARMACOLOGY and Clinical Studies]. ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis.

Because the dosage of ONGLYZA should be limited to 2.5 mg based upon renal function, assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter. Renal function can be estimated from serum creatinine using the Cockcroft-Gault formula or Modification of Diet in Renal Disease formula. [See CLINICAL PHARMACOLOGY.]

Dosage Adjustment with Concomitant Use of Strong CYP3A4/5 Inhibitors

The dosage of ONGLYZA is 2.5 mg once daily when coadministered with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). [See DRUG INTERACTIONS andCLINICAL PHARMACOLOGY.]

Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin

When ONGLYZA is used in combination with an insulin secretagogue (e.g.,sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia. [SeeWARNINGS AND PRECAUTIONS]

How Supplied

Dosage Forms And Strengths

  • ONGLYZA (saxagliptin) 5 mg tablets are pink, biconvex, round, film-coated tablets with “5” printed on one side and “4215” printed on the reverse side, in blue ink.
  • ONGLYZA (saxagliptin) 2.5 mg tablets are pale yellow to light yellow, biconvex, round, film-coated tablets with “2.5” printed on one side and “4214” printed on the reverse side, in blue ink.

ONGLYZA® (saxagliptin) tablets have markings on both sides and are available in the strengths and packages listed in Table 14.

Table 14: ONGLYZA Tablet Presentations

TABLET STRENGTH FILM-COATED TABLET COLOR/SHAPE TABLET MARKINGS PACKAGE SIZE NDC CODE
5 mg pink biconvex, round “5” on one side and “4215” on the reverse, in blue ink Bottles of 30 0003-4215-11
Bottles of 90 0003-4215-21
Bottles of 500 0003-4215-31
Blister of 100 0003-4215-41
2.5 mg pale yellow to light yellow biconvex, round “2.5” on one side and “4214” on the reverse, in blue ink Bottles of 30 0003-4214-11
Bottles of 90 0003-4214-21

 

Storage and Handling

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Manufactured by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Marketed by: Bristol-Myers Squibb Company, Princeton, NJ 08543 and AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850.. Rev May 2013

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions,adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions with Monotherapy and with Add-On Combination Therapy

In two placebo-controlled monotherapy trials of 24-weeks duration, patients were treated with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, and placebo. Three 24-week, placebocontrolled, add-on combination therapy trials were also conducted: one with metformin, one with a thiazolidinedione(pioglitazone or rosiglitazone), and one with glyburide. In these three trials, patients were randomized to add-on therapy with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, or placebo. A saxagliptin 10 mg treatment arm was included in one of the monotherapy trials and in the add-on combination trial with metformin. The 10 mg dosage is not an approved dosage.

In a prespecified pooled analysis of the 24-week data (regardless of glycemic rescue) from the two monotherapy trials, the add-on to metformin trial, the add-on to thiazolidinedione (TZD) trial, and the add-on to glyburide trial, the overall incidence of adverse events in patients treated with ONGLYZA 2.5 mg and ONGLYZA 5 mg was similar to placebo (72% and 72.2% versus 70.6%, respectively). Discontinuation of therapy due to adverse events occurred in 2.2%, 3.3%, and 1.8% of patients receiving ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. The most common adverse events (reported in at least 2 patients treated with ONGLYZA 2.5 mg or at least 2 patients treated with ONGLYZA 5 mg) associated with premature discontinuation of therapy included lymphopenia (0.1% and 0.5% versus 0%, respectively), rash (0.2% and 0.3% versus 0.3%), blood creatinine increased (0.3% and 0% versus 0%), and bloodcreatine phosphokinase increased (0.1% and 0.2% versus 0%). The adverse reactions in this pooled analysis reported (regardless of investigator assessment of causality) in ≥ 5% of patients treated with ONGLYZA 5 mg, and more commonly than in patients treated with placebo are shown in Table 1.

Table 1: Adverse Reactions in Placebo-Controlled Trials* Reported in ≥ 5% of Patients Treated with ONGLYZA 5 mg and More Commonly than in Patients Treated with Placebo

  NUMBER (%) OF PATIENTS
ONGLYZA 5 MG PLACEBO
N=799
Upper respiratory tract infection 68 (7.7) 61 (7.6)
Urinary tract infection 60 (6.8) 49 (6.1)
Headache 57 (6.5) 47 (5.9)
* The 5 placebo-controlled trials include two monotherapy trials and one add-on combination therapy trial with each of the following: metformin, thiazolidinedione, or glyburide. Table shows 24-week data regardless of glycemic rescue.

 

In patients treated with ONGLYZA 2.5 mg, headache (6.5%) was the only adverse reaction reported at a rate ≥ 5% and more commonly than in patients treated with placebo. In this pooled analysis, adverse reactions that were reported in ≥ 2% of patients treated with ONGLYZA 2.5 mg or ONGLYZA 5 mg and ≥ 1% more frequently compared to placebo included:sinusitis (2.9% and 2.6% versus 1.6%, respectively), abdominal pain (2.4% and 1.7% versus 0.5%), gastroenteritis (1.9% and 2.3% versus 0.9%), and vomiting (2.2% and 2.3% versus 1.3%).

In the add-on to TZD trial, the incidence of peripheral edema was higher for ONGLYZA 5 mg versus placebo (8.1% and 4.3%, respectively). The incidence of peripheral edema for ONGLYZA 2.5 mg was 3.1%. None of the reported adverse reactions of peripheral edema resulted in study drug discontinuation. Rates of peripheral edema for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo were 3.6% and 2% versus 3% given as monotherapy, 2.1% and 2.1% versus 2.2% given as add-on therapy to metformin, and 2.4% and 1.2% versus 2.2% given as add-on therapy to glyburide.

The incidence rate of fractures was 1.0 and 0.6 per 100 patient-years, respectively, for ONGLYZA (pooled analysis of 2.5 mg, 5 mg, and 10 mg) and placebo. The 10 mg dosage is not an approved dosage. The incidence rate of fracture events in patients who received ONGLYZA did not increase over time. Causality has not been established and nonclinical studies have not demonstrated adverse effects of ONGLYZA on bone.

An event of thrombocytopenia, consistent with a diagnosis of idiopathic thrombocytopenic purpura, was observed in the clinical program. The relationship of this event to ONGLYZA is not known.

Adverse Reactions in Patients with Renal Impairment

ONGLYZA 2.5 mg was compared to placebo in a 12-week trial in 170 patients with type 2 diabetes and moderate or severe renal impairment orend-stage renal disease (ESRD). The incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo.

Adverse Reactions with Concomitant Use with Insulin

In the add-on to insulin trial [see Clinical Studies], the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo, except for confirmed hypoglycemia [see ADVERSE REACTIONS].

Adverse Reactions with Concomitant Use with Metformin in Treatment-Naïve Patients with Type 2 Diabetes

Table 2 shows the adverse reactions reported (regardless of investigator assessment of causality) in ≥ 5% of patients participating in an additional 24-week, active-controlled trial of coadministered ONGLYZA and metformin in treatment-naive patients.

Table 2: Initial Therapy with Combination of ONGLYZA and Metformin in Treatment-Naive Patients: Adverse Reactions Reported in ≥ 5% of Patients Treated with Combination Therapy of ONGLYZA 5 mg Plus Metformin (and More Commonly than in Patients Treated with Metformin Alone)

  NUMBER (%) OF PATIENTS
ONGLYZA 5 MG + METFORMIN*
N=320
METFORMIN*
N=328
Headache 24 (7.5) 17 (5.2)
Nasopharyngitis 22 (6.9) 13 (4.0)
* Metformin was initiated at a starting dose of 500 mg daily and titrated up to a maximum of 2000 mg daily.

 

Hypoglycemia

Adverse reactions of hypoglycemia were based on all reports of hypoglycemia. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.

In the add-on to glyburide study, the overall incidence of reported hypoglycemia was higher for ONGLYZA 2.5 mg and ONGLYZA 5 mg (13.3% and 14.6%) versus placebo (10.1%). The incidence of confirmed hypoglycemia in this study, defined as symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤ 50 mg/dL, was 2.4% and 0.8% for ONGLYZA 2.5 mg and ONGLYZA 5 mg and 0.7% for placebo [seeWARNINGS AND PRECAUTIONS]. The incidence of reported hypoglycemia for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo given as monotherapy was 4% and 5.6% versus 4.1%, respectively, 7.8% and 5.8% versus 5% given as add-on therapy to metformin, and 4.1% and 2.7% versus 3.8% given as addon therapy to TZD. The incidence of reported hypoglycemia was 3.4% in treatment-naïve patients given ONGLYZA 5 mg plus metformin and 4% in patients given metformin alone. In the active-controlled trial comparing add-on therapy with ONGLYZA 5 mg to glipizide in patients inadequately controlled on metformin alone, the incidence of reported hypoglycemia was 3% (19 events in 13 patients) with ONGLYZA 5 mg versus 36.3% (750 events in 156 patients) with glipizide. Confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤ 50 mg/dL) was reported in none of the ONGLYZA-treated patients and in 35 glipizide-treated patients (8.1%) (p < 0.0001).

During 12 weeks of treatment in patients with moderate or severe renal impairment or ESRD, the overall incidence of reported hypoglycemia was 20% among patients treated with ONGLYZA 2.5 mg and 22% among patients treated with placebo. Four ONGLYZA-treated patients (4.7%) and three placebo-treated patients (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤ 50 mg/dL).

In the add-on to insulin trial, the overall incidence of reported hypoglycemia was 18.4% for ONGLYZA 5 mg and 19.9% for placebo. However, the incidence of confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤ 50 mg/dL) was higher with ONGLYZA 5 mg (5.3%) versus placebo (3.3%).

In the add-on to metformin plus sulfonylurea trial, the overall incidence of reported hypoglycemia was 10.1% for ONGLYZA 5 mg and 6.3% for placebo. Confirmed hypoglycemia was reported in 1.6% of the ONGLYZA-treated patients and in none of the placebo-treated patients [seeWARNINGS AND PRECAUTIONS].

Hypersensitivity Reactions

Hypersensitivity-related events, such as urticaria and facial edema in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients who received ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. None of these events in patients who received ONGLYZA required hospitalization or were reported as life-threatening by the investigators. One ONGLYZA-treated patient in this pooled analysis discontinued due to generalized urticaria and facial edema.

Infections

In the unblinded, controlled, clinical trial database for ONGLYZA to date, there have been 6 (0.12%) reports of tuberculosis among the 4959 ONGLYZA-treated patients (1.1 per 1000 patient-years) compared to no reports of tuberculosis among the 2868 comparator-treated patients. Two of these six cases were confirmed with laboratory testing. The remaining cases had limited information or had presumptive diagnoses of tuberculosis. None of the six cases occurred in the United States or in Western Europe. One case occurred in Canada in a patient originally from Indonesia who had recently visited Indonesia. The duration of treatment with ONGLYZA until report of tuberculosis ranged from 144 to 929 days. Post-treatmentlymphocyte counts were consistently within the reference range for four cases. One patient had lymphopenia prior to initiation of ONGLYZA that remained stable throughout ONGLYZA treatment. The final patient had an isolated lymphocyte count below normal approximately four months prior to the report of tuberculosis. There have been no spontaneous reports of tuberculosis associated with ONGLYZA use. Causality has not been estimated and there are too few cases to date to determine whether tuberculosis is related to ONGLYZA use.

There has been one case of a potential opportunistic infection in the unblinded, controlled clinical trial database to date in an ONGLYZA-treated patient who developed suspected foodborne fatal salmonella sepsis after approximately 600 days of ONGLYZA therapy. There have been no spontaneous reports of opportunistic infections associated with ONGLYZA use.

Vital Signs

No clinically meaningful changes in vital signs have been observed in patients treated with ONGLYZA.

Laboratory Tests

Absolute Lymphocyte Counts

There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤ 750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the ONGLYZA 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA. The decreases in lymphocyte count were not associated with clinically relevant adverse reactions. The 10 mg dosage is not an approved dosage.

The clinical significance of this decrease in lymphocyte count relative to placebo is not known. When clinically indicated, such as in settings of unusual or prolonged infection, lymphocyte count should be measured. The effect of ONGLYZA on lymphocyte counts in patients with lymphocyte abnormalities (e.g., human immunodeficiency virus) is unknown.

Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of ONGLYZA. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions. [See CONTRAINDICATIONS andWARNINGS AND PRECAUTIONS]
  • Acute pancreatitis. [See INDICATIONS AND USAGE and WARNINGS AND PRECAUTIONS]

Read the Onglyza (saxagliptin tablets) Side Effects Center for a complete guide to possible side effects

Learn More »
 
 
 

Interactions

Strong Inhibitors of CYP3A4/5 Enzymes

Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). The dose of ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor. [See DOSAGE AND ADMINISTRATIONand CLINICAL PHARMACOLOGY.]

Read the Onglyza Drug Interactions Center for a complete guide to possible interactions

Learn More »
 

This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Pancreatitis

There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. After initiation of ONGLYZA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, ONGLYZA should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA.

Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin

When ONGLYZA was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. [See ADVERSE REACTIONS] Therefore, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with ONGLYZA. [SeeDOSAGE AND ADMINISTRATION.]

Hypersensitivity Reactions

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with ONGLYZA. These reactions include anaphylaxis,angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with ONGLYZA, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute alternative treatment for diabetes. [SeeADVERSE REACTIONS.]

Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with ONGLYZA.

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence ofmacrovascular risk reduction with ONGLYZA or any other antidiabetic drug.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide).

Medication Guide

Healthcare providers should instruct their patients to read the Medication Guide before starting ONGLYZA therapy and to reread it each time the prescription is renewed. Patients should be instructed to inform their healthcare provider if they develop any unusual symptom or if any existing symptom persists or worsens.

Patients should be informed of the potential risks and benefits of ONGLYZA and of alternative modes of therapy. Patients should also be informed about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1C testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and patients should be advised to seek medical advice promptly.

Pancreatitis

Patients should be informed that acute pancreatitis has been reported during postmarketing use of ONGLYZA. Before initiating ONGLYZA, patients should be questioned about other risk factors for pancreatitis, such as a history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. Patients should also be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue ONGLYZA and contact their healthcare provider if persistent severe abdominal pain occurs [see WARNINGS AND PRECAUTIONS].

Hypersensitivity Reactions

Patients should be informed that serious allergic (hypersensitivity) reactions, such as angioedema, anaphylaxis, and exfoliative skin conditions, have been reported during postmarketing use of ONGLYZA. If symptoms of these allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking ONGLYZA and seek medical advice promptly.

Missed Dose

Patients should be informed that if they miss a dose of ONGLYZA they should take the next dose as prescribed, unless otherwise instructed by their healthcare provider. Patients should be instructed not to take an extra dose the next day.

Administration Instructions

Patients should be informed that ONGLYZA tablets must not be split or cut.

Laboratory Tests

Patients should be informed that response to all diabetic therapies should be monitored by periodic measurements of blood glucose and A1C, with a goal of decreasing these levels toward the normal range. A1C is especially useful for evaluating long-term glycemic control. Patients should be informed of the potential need to adjust their dose based on changes in renal function tests over time.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Saxagliptin did not induce tumors in either mice (50, 250, and 600 mg/kg) or rats (25, 75, 150, and 300 mg/kg) at the highest doses evaluated. The highest doses evaluated in mice were equivalent to approximately 870 (males) and 1165 (females) times the human exposure at the MRHD of 5 mg/day. In rats, exposures were approximately 355 (males) and 2217 (females) times the MRHD.

Mutagenesis

Saxagliptin was not mutagenic or clastogenic with or without metabolic activation in an in vitro Ames bacterial assay, an in vitro cytogenetics assay in primary human lymphocytes, an in vivo oral micronucleus assay in rats, an in vivo oral DNA repair study in rats, and an oral in vivo/in vitro cytogenetics study in rat peripheral blood lymphocytes. The active metabolite was not mutagenic in an in vitro Ames bacterial assay.

Impairment of Fertility

In a rat fertility study, males were treated with oral gavage doses for 2 weeks prior to mating, during mating, and up to scheduled termination (approximately 4 weeks total) and females were treated with oral gavage doses for 2 weeks prior to mating through gestation day 7. No adverse effects on fertility were observed at exposures of approximately 603 (males) and 776 (females) times the MRHD. Higher doses that elicited maternal toxicity also increased fetal resorptions (approximately 2069 and 6138 times the MRHD). Additional effects on estrous cycling, fertility, ovulation, andimplantation were observed at approximately 6138 times the MRHD.

Use In Specific Populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if clearly needed.

Saxagliptin was not teratogenic at any dose tested when administered to pregnant rats and rabbits during periods of organogenesis. Incompleteossification of the pelvis, a form of developmental delay, occurred in rats at a dose of 240 mg/kg, or approximately 1503 and 66 times human exposure to saxagliptin and the active metabolite, respectively, at the maximum recommended human dose (MRHD) of 5 mg. Maternal toxicity and reduced fetal body weights were observed at 7986 and 328 times the human exposure at the MRHD for saxagliptin and the active metabolite, respectively. Minor skeletal variations in rabbits occurred at a maternally toxic dose of 200 mg/kg, or approximately 1432 and 992 times the MRHD.

Coadministration of saxagliptin and metformin, to pregnant rats and rabbits during the period of organogenesis, was neither embryolethal nor teratogenic in either species when tested at doses yielding systemic exposures (AUC) up to 100 and 10 times the MRHD (saxagliptin 5 mg and metformin 2000 mg), respectively, in rats; and 249 and 1.1 times the MRHDs in rabbits. In rats, minor developmental toxicity was limited to an increased incidence of wavy ribs; associated maternal toxicity was limited to weight decrements of 11% to 17% over the course of the study, and related reductions in maternal food consumption. In rabbits, coadministration was poorly tolerated in a subset of mothers (12 of 30), resulting in death, moribundity, or abortion. However, among surviving mothers with evaluable litters, maternal toxicity was limited to marginal reductions in body weight over the course of gestation days 21 to 29; and associated developmental toxicity in these litters was limited to fetal body weight decrements of 7%, and a low incidence of delayed ossification of the fetal hyoid.

Saxagliptin administered to female rats from gestation day 6 to lactation day 20 resulted in decreased body weights in male and female offspring only at maternally toxic doses (exposures ≥ 1629 and 53 times saxagliptin and its active metabolite at the MRHD). No functional or behavioral toxicity was observed in offspring of rats administered saxagliptin at any dose.

Saxagliptin crosses the placenta into the fetus following dosing in pregnant rats.

Nursing Mothers

Saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. It is not known whether saxagliptin is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of ONGLYZA in pediatric patients under 18 years of age have not been established. Additionally, studies characterizing the pharmacokinetics of ONGLYZA in pediatric patients have not been performed.

Geriatric Use

In the six, double-blind, controlled clinical safety and efficacy trials of ONGLYZA, 634 (15.3%) of the 4148 randomized patients were 65 years and over, and 59 (1.4%) patients were 75 years and over. No overall differences in safety or effectiveness were observed between patients ≥ 65 years old and the younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

Saxagliptin and its active metabolite are eliminated in part by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function. [See DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]

This monograph has been modified to include the generic and brand name in many instances.

OverDose

In a controlled clinical trial, once-daily, orally-administered ONGLYZA in healthy subjects at doses up to 400 mg daily for 2 weeks (80 times the MRHD) had no dose-related clinical adverse reactions and no clinically meaningful effect on QTc interval or heart rate.

In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient's clinical status. Saxagliptin and its active metabolite are removed by hemodialysis (23% of dose over 4 hours).

ContrainDications

ONGLYZA is contraindicated in patients with a history of a serious hypersensitivity reaction to ONGLYZA, such as anaphylaxis, angioedema, or exfoliative skin conditions. [See WARNINGS AND PRECAUTIONS andADVERSE REACTIONS]

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.

Pharmacodynamics

In patients with type 2 diabetes mellitus, administration of ONGLYZA inhibits DPP4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased glucose-dependent insulin secretion from pancreatic beta cells. The rise in insulin and decrease in glucagon were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.

Cardiac Electrophysiology

In a randomized, double-blind, placebo-controlled, 4-way crossover, active comparator study using moxifloxacin in 40 healthy subjects, ONGLYZA was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 40 mg (8 times the MRHD).

Pharmacokinetics

The pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin were similar in healthy subjects and in patients with type 2 diabetes mellitus. The Cmax and AUC values of saxagliptin and its active metabolite increased proportionally in the 2.5 to 400 mg dose range. Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. The average variability (%CV) for AUC and Cmax for both saxagliptin and its active metabolite was less than 25%.

No appreciable accumulation of either saxagliptin or its active metabolite was observed with repeated once-daily dosing at any dose level. No dose- and time-dependence were observed in the clearance of saxagliptin and its active metabolite over 14 days of once-daily dosing with saxagliptin at doses ranging from 2.5 to 400 mg.

Absorption

The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Administration with a high-fat meal resulted in an increase in Tmax of saxagliptin by approximately 20 minutes as compared to fasted conditions. There was a 27% increase in the AUC of saxagliptin when given with a meal as compared to fasted conditions. ONGLYZA may be administered with or without food.

Distribution

The in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible. Therefore, changes in blood protein levels in various disease states (e.g., renal or hepatic impairment) are not expected to alter the disposition of saxagliptin.

Metabolism

The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). The major metabolite of saxagliptin is also a DPP4 inhibitor, which is one-half as potent as saxagliptin. Therefore, strong CYP3A4/5 inhibitors and inducers will alter the pharmacokinetics of saxagliptin and its active metabolite. [See DRUG INTERACTIONS]

Excretion

Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. The average renal clearance of saxagliptin (~230 mL/min) was greater than the average estimated glomerular filtration rate (~120 mL/min), suggesting some active renal excretion. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from thegastrointestinal tract. Following a single oral dose of ONGLYZA 5 mg to healthy subjects, the mean plasma terminal half-life (t½) for saxagliptin and its active metabolite was 2.5 and 3.1 hours, respectively.

Specific Populations

Renal Impairment

A single-dose, open-label study was conducted to evaluate the pharmacokinetics of saxagliptin (10 mg dose) in subjects with varying degrees of chronic renal impairment (N=8 per group) compared to subjects with normal renal function. The 10 mg dosage is not an approved dosage. The study included patients with renal impairment classified on the basis of creatinine clearance as mild ( > 50 to ≤ 80 mL/min), moderate (30 to ≤ 50 mL/min), and severe ( < 30 mL/min), as well as patients with end-stage renal disease on hemodialysis. Creatinine clearance was estimated from serum creatinine based on the Cockcroft-Gault formula:

 

Males: (weight in kg) x (140 – age)
(72) x serum creatinine (mg/100 mL)
Females (0.85) x (above value)

 

The degree of renal impairment did not affect the Cmax of saxagliptin or its active metabolite. In subjects with mild renal impairment, the AUC values of saxagliptin and its active metabolite were 20% and 70% higher, respectively, than AUC values in subjects with normal renal function. Because increases of this magnitude are not considered to be clinically relevant, dosage adjustment in patients with mild renal impairment is not recommended. In subjects with moderate or severe renal impairment, the AUC values of saxagliptin and its active metabolite were up to 2.1- and 4.5-fold higher, respectively, than AUC values in subjects with normal renal function. To achieve plasma exposures of saxagliptin and its active metabolite similar to those in patients with normal renal function, the recommended dose is 2.5 mg once daily in patients with moderate and severe renal impairment, as well as in patients with end-stage renal disease requiring hemodialysis. Saxagliptin is removed by hemodialysis.

Hepatic Impairment

In subjects with hepatic impairment (Child-Pugh classes A, B, and C), mean Cmax and AUC of saxagliptin were up to 8% and 77% higher, respectively, compared to healthy matched controls following administration of a single 10 mg dose of saxagliptin. The 10 mg dosage is not an approved dosage. The corresponding Cmax and AUC of the active metabolite were up to 59% and 33% lower, respectively, compared to healthy matched controls. These differences are not considered to be clinically meaningful. No dosage adjustment is recommended for patients with hepatic impairment.

Body Mass Index

No dosage adjustment is recommended based on body mass index (BMI) which was not identified as a significant covariate on the apparent clearance of saxagliptin or its active metabolite in the population pharmacokinetic analysis.

Gender

No dosage adjustment is recommended based on gender. There were no differences observed in saxagliptin pharmacokinetics between males and females. Compared to males, females had approximately 25% higher exposure values for the active metabolite than males, but this difference is unlikely to be of clinical relevance. Gender was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.

Geriatric

No dosage adjustment is recommended based on age alone. Elderly subjects (65-80 years) had 23% and 59% higher geometric mean Cmax and geometric mean AUC values, respectively, for saxagliptin than young subjects (18-40 years). Differences in active metabolite pharmacokinetics between elderly and young subjects generally reflected the differences observed in saxagliptin pharmacokinetics. The difference between the pharmacokinetics of saxagliptin and the active metabolite in young and elderly subjects is likely due to multiple factors including declining renal function and metabolic capacity with increasing age. Age was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.

Race and Ethnicity

No dosage adjustment is recommended based on race. The population pharmacokinetic analysis compared the pharmacokinetics of saxagliptin and its active metabolite in 309 Caucasian subjects with 105 non-Caucasian subjects (consisting of six racial groups). No significant difference in the pharmacokinetics of saxagliptin and its active metabolite were detected between these two populations.

Drug-Drug Interaction Studies

In Vitro Assessment of Drug Interactions

The metabolism of saxagliptin is primarily mediated by CYP3A4/5.

In in vitro studies, saxagliptin and its active metabolite did not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, or 3A4. Therefore, saxagliptin is not expected to alter the metabolic clearance of coadministered drugs that are metabolized by these enzymes. Saxagliptin is a P-glycoprotein (P-gp) substrate but is not a significant inhibitor or inducer of P-gp.

In Vivo Assessment of Drug Interactions

Table 3: Effect of Coadministered Drugs on Systemic Exposures of Saxagliptin and its Active Metabolite, 5-hydroxy Saxagliptin

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Table 4: Effect of Saxagliptin on Systemic Exposures of Coadministered Drugs

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Animal Toxicology and/or Pharmacology

Saxagliptin produced adverse skin changes in the extremities of cynomolgus monkeys (scabs and/or ulceration of tail, digits, scrotum, and/or nose). Skin lesions were reversible at ≥ 20 times the MRHD but in some cases were irreversible and necrotizing at higher exposures. Adverse skin changes were not observed at exposures similar to (1 to 3 times) the MRHD of 5 mg. Clinical correlates to skin lesions in monkeys have not been observed in human clinical trials of saxagliptin.

Clinical Studies

ONGLYZA has been studied as monotherapy and in combination with metformin, glyburide, and thiazolidinedione (pioglitazone and rosiglitazone) therapy.

A total of 4148 patients with type 2 diabetes mellitus were randomized in six, double-blind, controlled clinical trials conducted to evaluate the safety and glycemic efficacy of ONGLYZA. A total of 3021 patients in these trials were treated with ONGLYZA. In these trials, the mean age was 54 years, and 71% of patients were Caucasian, 16% were Asian, 4% were black, and 9% were of other racial groups. An additional 423 patients, including 315 who received ONGLYZA, participated in a placebo-controlled, dose-ranging study of 6 to 12 weeks in duration.

In these six, double-blind trials, ONGLYZA was evaluated at doses of 2.5 mg and 5 mg once daily. Three of these trials also evaluated a saxagliptin dose of 10 mg daily. The 10 mg daily dose of saxagliptin did not provide greater efficacy than the 5 mg daily dose. The 10 mg dosage is not an approved dosage. Treatment with ONGLYZA 5 mg and 2.5 mg doses produced clinically relevant and statistically significant improvements in hemoglobin A1c (A1C), fasting plasma glucose (FPG), and 2-hour postprandial glucose (PPG) following a standard oral glucose tolerance test (OGTT), compared to control. Reductions in A1C were seen across subgroups including gender, age, race, and baseline BMI.

ONGLYZA was not associated with significant changes from baseline in body weight or fasting serum lipids compared to placebo.

ONGLYZA has also been evaluated in four additional trials in patients with type 2 diabetes: an active-controlled trial comparing add-on therapy with ONGLYZA to glipizide in 858 patients inadequately controlled on metformin alone, a trial comparing ONGLYZA to placebo in 455 patients inadequately controlled on insulin alone or on insulin in combination with metformin, a trial comparing ONGLYZA to placebo in 257 patients inadequately controlled on metformin plus a sulfonylurea, and a trial comparing ONGLYZA to placebo in 170 patients with type 2 diabetes and moderate or severe renal impairment or ESRD.

Monotherapy

A total of 766 patients with type 2 diabetes inadequately controlled on diet and exercise (A1C ≥ 7% to ≤ 10%) participated in two 24-week, double-blind, placebo-controlled trials evaluating the efficacy and safety of ONGLYZA monotherapy.

In the first trial, following a 2-week single-blind diet, exercise, and placebo lead-in period, 401 patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy, added on to placebo or ONGLYZA. Efficacy was evaluated at the last measurement prior to rescue therapy for patients needing rescue. Dose titration of ONGLYZA was not permitted.

Treatment with ONGLYZA 2.5 mg and 5 mg daily provided significant improvements in A1C, FPG, and PPG compared to placebo (Table 5). The percentage of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 16% in the ONGLYZA 2.5 mg treatment group, 20% in the ONGLYZA 5 mg treatment group, and 26% in the placebo group.

Table 5: Glycemic Parameters at Week 24 in a Placebo-Controlled Study of ONGLYZA Monotherapy in Patients with Type 2 Diabetes*

EFFICACY PARAMETER ONGLYZA 2.5 MG
N=102
ONGLYZA 5 MG
N=106
PLACEBO 
N=95
Hemoglobin A1C (%) N=100 N=103 N=92
Baseline (mean) 7.9 8.0 7.9
Change from baseline (adjusted mean†) -0.4 -0.5 +0.2
Difference from placebo (adjusted mean†) −0.6‡ −0.6‡  
   95% Confidence Interval (-0.9, -0.3) (-0.9, -0.4)  
Percent of patients achieving A1C < 7% 35% (35/100) 38%§ (39/103) 24% (22/92)
Fasting Plasma Glucose (mg/dL) N=101 N=105 N=92
Baseline (mean) 178 171 172
Change from baseline (adjusted mean†) -15 -9 +6
Difference from placebo (adjusted mean†) -21§ -15§  
  95% Confidence Interval (-31, -10) (-25, -4)  
2-hour Postprandial Glucose (mg/dL) N=78 N=84 N=71
Baseline (mean) 279 278 283
Change from baseline (adjusted mean†) -45 -43 -6
Difference from placebo (adjusted mean†) -391¶ -37§  
   95% Confidence Interval (-61, -16) (-59, -15)  
* Intent-to-treat population using last observation on study or last observation prior to metformin rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo
§ p-value < 0.05 compared to placebo
¶ Significance was not tested for the 2-hour PPG for the 2.5 mg dose of ONGLYZA.

 

A second 24-week monotherapy trial was conducted to assess a range of dosing regimens for ONGLYZA. Treatment-naive patients with inadequately controlled diabetes (A1C ≥ 7% to ≤ 10%) underwent a 2-week, single-blind diet, exercise, and placebo lead-in period. A total of 365 patients were randomized to 2.5 mg every morning, 5 mg every morning, 2.5 mg with possible titration to 5 mg every morning, or 5 mg every evening of ONGLYZA, or placebo.

Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy added on to placebo or ONGLYZA; the number of patients randomized per treatment group ranged from 71 to 74.

Treatment with either ONGLYZA 5 mg every morning or 5 mg every evening provided significant improvements in A1C versus placebo (mean placebo-corrected reductions of -0.4% and -0.3%, respectively). Treatment with ONGLYZA 2.5 mg every morning also provided significant improvement in A1C versus placebo (mean placebo-corrected reduction of -0.4%).

Combination Therapy

Add-On Combination Therapy with Metformin

A total of 743 patients with type 2 diabetes participated in this 24-week, randomized, doubleblind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin in patients with inadequate glycemic control (A1C ≥ 7% and ≤ 10%) on metformin alone. To qualify for enrollment, patients were required to be on a stable dose of metformin (1500-2550 mg daily) for at least 8 weeks.

Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin at their pre-study dose, up to 2500 mg daily. Following the lead-in period, eligible patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo in addition to their current dose of open-label metformin. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with pioglitazone rescue therapy, added on to existing study medications. Dose titrations of ONGLYZA and metformin were not permitted.

ONGLYZA 2.5 mg and 5 mg add-on to metformin provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin (Table 6). Mean changes from baseline for A1C over time and at endpoint are shown in Figure 1. The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 15% in the ONGLYZA 2.5 mg add-on to metformin group, 13% in the ONGLYZA 5 mg add-on to metformin group, and 27% in the placebo add-on to metformin group.

Table 6: Glycemic Parameters at Week 24 in a Placebo-Controlled Study of ONGLYZA as Add-On Combination Therapy with Metformin*

EFFICACY PARAMETER ONGLYZA 2.5 MG + METFORMIN 
N=192
ONGLYZA 5 MG + METFORMIN 
N=191
PLACEBO + METFORMIN 
N=179
Hemoglobin A1C (%) N=186 N=186 N=175
Baseline (mean) 8.1 8.1 8.1
Change from baseline (adjusted mean†) -0.6 -0.7 +0.1
Difference from placebo (adjusted mean†) -0.7* -0.8*  
  95% Confidence Interval (-0.9, -0.5) (-1.0, -0.6)  
Percent of patients achieving A1C < 7% 37%§ (69/186) 44%§ (81/186) 17% (29/175)
Fasting Plasma Glucose (mg/dL) N=188 N=187 N=176
Baseline (mean) 174 179 175
Change from baseline (adjusted mean†) -14 -22 +1
Difference from placebo (adjusted mean†) -16§ -23§  
  95% Confidence Interval (-23, -9) (-30, -16)  
2-hour Postprandial Glucose (mg/dL) N=155 N=155 N=135
Baseline (mean) 294 296 295
Change from baseline (adjusted mean†) -62 -58 -18
Difference from placebo (adjusted mean†) -44§ -40§  
  95% Confidence Interval (-60, -27) (-56, -24)  
* Intent-to-treat population using last observation on study or last observation prior to pioglitazone rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo + metformin
§ p-value < 0.05 compared to placebo + metformin

 

Figure 1: Mean Change from Baseline in A1C in a Placebo-Controlled Trial of ONGLYZA as Add-On Combination Therapy with Metformin*

View Enlarged Table

 

* Includes patients with a baseline and week 24 value.
Week 24 (LOCF) includes intent-to-treat population using last observation on study prior to pioglitazone rescue therapy for patients needing rescue. Mean change from baseline is adjusted for baseline value.

Add-On Combination Therapy with a Thiazolidinedione

A total of 565 patients with type 2 diabetes participated in this 24-week, randomized, doubleblind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a thiazolidinedione (TZD) in patients with inadequate glycemic control (A1C ≥ 7% to ≤ 10.5%) on TZD alone. To qualify for enrollment, patients were required to be on a stable dose of pioglitazone (30-45 mg once daily) or rosiglitazone (4 mg once daily or 8 mg either once daily or in two divided doses of 4 mg) for at least 12 weeks.

Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received TZD at their pre-study dose. Following the lead-in period, eligible patients were randomized to 2.5 mg or 5 mg of ONGLYZA or placebo in addition to their current dose of TZD. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medications. Dose titration of ONGLYZA or TZD was not permitted during the study. A change in TZD regimen from rosiglitazone to pioglitazone at specified, equivalent therapeutic doses was permitted at the investigator's discretion if believed to be medically appropriate.

ONGLYZA 2.5 mg and 5 mg add-on to TZD provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to TZD (Table 7). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 10% in the ONGLYZA 2.5 mg add-on to TZD group, 6% for the ONGLYZA 5 mg add-on to TZD group, and 10% in the placebo add-on to TZD group.

Table 7: Glycemic Parameters at Week 24 in a Placebo-Controlled Study of ONGLYZA as Add-On Combination Therapy with a Thiazolidinedione*

EFFICACY PARAMETER ONGLYZA 2.5 MG+ TZD
N=195
ONGLYZA 5 MG+ TZD
N=186
PLACEBO+ TZD
Hemoglobin A1C (%) N=192 N=183 N=180
Baseline (mean) 8.3 8.4 8.2
Change from baseline (adjusted mean†) -0.7 -0.9 -0.3
Difference from placebo (adjusted mean†) -0.4§ −0.6‡  
  95% Confidence Interval (-0.6, -0.2) (-0.8, -0.4)  
Percent of patients achieving A1C < 7% 42%§ (81/192) 42%§ (77/184) 26% (46/180)
Fasting Plasma Glucose (mg/dL) N=193 N=185 N=181
Baseline (mean) 163 160 162
Change from baseline (adjusted mean†) -14 -17 -3
Difference from placebo (adjusted mean†) -12§ -15§  
  95% Confidence Interval (-20, -3) (-23, -6)  
2-hour Postprandial Glucose (mg/dL) N=156 N=134 N=127
Baseline (mean) 296 303 291
Change from baseline (adjusted mean†) -55 -65 -15
Difference from placebo (adjusted mean†) -40§ -50§  
  95% Confidence Interval (-56, -24) (-66, -34)  
* Intent-to-treat population using last observation on study or last observation prior to metformin rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo + TZD
§ p-value < 0.05 compared to placebo + TZD

 

Add-On Combination Therapy with Glyburide

A total of 768 patients with type 2 diabetes participated in this 24-week, randomized, doubleblind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a sulfonylurea (SU) in patients with inadequate glycemic control at enrollment (A1C ≥ 7.5% to ≤ 10%) on a submaximal dose of SU alone. To qualify for enrollment, patients were required to be on a submaximal dose of SU for 2 months or greater. In this study, ONGLYZA in combination with a fixed, intermediate dose of SU was compared to titration to a higher dose of SU.

Patients who met eligibility criteria were enrolled in a single-blind, 4-week, dietary and exercise lead-in period, and placed on glyburide 7.5 mg once daily. Following the lead-in period, eligible patients with A1C ≥ 7% to ≤ 10% were randomized to either 2.5 mg or 5 mg of ONGLYZA addon to 7.5 mg glyburide or to placebo plus a 10 mg total daily dose of glyburide. Patients who received placebo were eligible to have glyburide up-titrated to a total daily dose of 15 mg. Up-titration of glyburide was not permitted in patients who received ONGLYZA 2.5 mg or 5 mg. Glyburide could be down-titrated in any treatment group once during the 24-week study period due tohypoglycemia as deemed necessary by the investigator. Approximately 92% of patients in the placebo plus glyburide group were up-titrated to a final total daily dose of 15 mg during the first 4 weeks of the study period. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medication. Dose titration of ONGLYZA was not permitted during the study.

In combination with glyburide, ONGLYZA 2.5 mg and 5 mg provided significant improvements in A1C, FPG, and PPG compared with the placebo plus up-titrated glyburide group (Table 8). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 18% in the ONGLYZA 2.5 mg add-on to glyburide group, 17% in the ONGLYZA 5 mg add-on to glyburide group, and 30% in the placebo plus up-titrated glyburide group.

Table 8: Glycemic Parameters at Week 24 in a Placebo-Controlled Study of ONGLYZA as Add-On Combination Therapy with Glyburide*

EFFICACY PARAMETER ONGLYZA 2.5 MG + GLYBURIDE 7.5 MG 
N=248
ONGLYZA 5 MG + GLYBURIDE 7.5 MG 
N=253
PLACEBO + UP-TITRATED GLYBURIDE
N=267
Hemoglobin A1C (%) N=246 N=250 N=264
Baseline (mean) 8.4 8.5 8.4
Change from baseline (adjusted mean†) -0.5 -0.6 +0.1
Difference from up-titrated glyburide (adjusted mean†) −0.6‡ −0.7‡  
  95% Confidence Interval (-0.8, -0.5) (-0.9, -0.6)  
Percent of patients achieving A1C < 7% 22%§ (55/246) 23%§ (57/250) 9% (24/264)
Fasting Plasma Glucose (mg/dL) N=247 N=252 N=265
Baseline (mean) 170 175 174
Change from baseline (adjusted mean†) -7 -10 +1
Difference from up-titrated glyburide (adjusted mean†) —8§ -10§  
  95% Confidence Interval (-14, —1) (-17, -4)  
2-hour Postprandial Glucose (mg/dL) N=195 N=202 N=206
Baseline (mean) 309 315 323
Change from baseline (adjusted mean†) -31 -34 +8
Difference from up-titrated glyburide (adjusted mean†) -38§ -42§  
  95% Confidence Interval (-50, -27) (-53, -31)  
* Intent-to-treat population using last observation on study or last observation prior to metformin rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo + up-titrated glyburide
§ p-value < 0.05 compared to placebo + up-titrated glyburide

 

Coadministration with Metformin in Treatment-Naive Patients

A total of 1306 treatment-naive patients with type 2 diabetes mellitus participated in this 24-week, randomized, double-blind, active-controlled trial to evaluate the efficacy and safety of ONGLYZA coadministered with metformin in patients with inadequate glycemic control (A1C ≥ 8% to ≤ 12%) on diet and exercise alone. Patients were required to be treatment-naive to be enrolled in this study.

Patients who met eligibility criteria were enrolled in a single-blind, 1-week, dietary and exercise placebo lead-in period. Patients were randomized to one of four treatment arms: ONGLYZA 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo, or metformin 500 mg + placebo. The 10 mg dosage is not an approved dosage. ONGLYZA was dosed once daily. In the 3 treatment groups using metformin, the metformin dose was up-titrated weekly in 500 mg per day increments, as tolerated, to a maximum of 2000 mg per day based on FPG. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue as add-on therapy.

Coadministration of ONGLYZA 5 mg plus metformin provided significant improvements in A1C, FPG, and PPG compared with placebo plus metformin (Table 9).

Table 9: Glycemic Parameters at Week 24 in a Placebo-Controlled Trial of ONGLYZA Coadministration with Metformin in Treatment-Naïve Patients*

EFFICACY PARAMETER ONGLYZA 5 MG + METFORMIN 
N=320
PLACEBO + METFORMIN 
N=328
Hemoglobin A1C (%) N=306 N=313
Baseline (mean) 9.4 9.4
Change from baseline (adjusted mean†) -2.5 -2.0
Difference from placebo + metformin (adjusted mean†) −0.5‡  
  95% Confidence Interval (-0.7, -0.4)  
Percent of patients achieving A1C < 7% 60%§ (185/307) 41% (129/314)
Fasting Plasma Glucose (mg/dL) N=315 N=320
Baseline (mean) 199 199
Change from baseline (adjusted mean†) -60 -47
Difference from placebo + metformin (adjusted mean†) -13s  
  95% Confidence Interval (-19, -6)  
2-hour Postprandial Glucose (mg/dL) N=146 N=141
Baseline (mean) 340 355
Change from baseline (adjusted mean†) -138 -97
Difference from placebo + metformin (adjusted mean†) -41§  
  95% Confidence Interval (-57, -25)  
* Intent-to-treat population using last observation on study or last observation prior to pioglitazone rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo + metformin
§ p-value < 0.05 compared to placebo + metformin

 

Add-On Combination Therapy with Metformin versus Glipizide Add-On Combination Therapy with Metformin

In this 52-week, active-controlled trial, a total of 858 patients with type 2 diabetes and inadequate glycemic control (A1C > 6.5% and ≤ 10%) on metformin alone were randomized to double-blind add-on therapy with ONGLYZA or glipizide. Patients were required to be on a stable dose of metformin (at least 1500 mg daily) for at least 8 weeks prior to enrollment.

Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin (1500-3000 mg based on their pre-study dose). Following the lead-in period, eligible patients were randomized to 5 mg of ONGLYZA or 5 mg of glipizide in addition to their current dose of open-label metformin. Patients in the glipizide plus metformin group underwent blinded titration of the glipizide dose during the first 18 weeks of the trial up to a maximum glipizide dose of 20 mg per day. Titration was based on a goal FPG ≤ 110 mg/dL or the highest tolerable glipizide dose. Fifty percent (50%) of the glipizide-treated patients were titrated to the 20-mg daily dose; 21% of the glipizidetreated patients had a final daily glipizide dose of 5 mg or less. The mean final daily dose of glipizide was 15 mg.

After 52 weeks of treatment, ONGLYZA and glipizide resulted in similar mean reductions from baseline in A1C when added to metformin therapy (Table 10). This conclusion may be limited to patients with baseline A1C comparable to those in the trial (91% of patients had baseline A1C < 9%).

From a baseline mean body weight of 89 kg, there was a statistically significant mean reduction of 1.1 kg in patients treated with ONGLYZA compared to a mean weight gain of 1.1 kg in patients treated with glipizide (p < 0.0001).

Table 10: Glycemic Parameters at Week 52 in an Active-Controlled Trial of ONGLYZA versus Glipizide in Combination with Metformin*

EFFICACY PARAMETER ONGLYZA 5 MG + METFORMIN 
N=428
TITRATED GLIPIZIDE + METFORMIN 
N=430
Hemoglobin A1C (%) N=423 N=423
Baseline (mean) 7.7 7.6
Change from baseline (adjusted mean†) -0.6 -0.7
Difference from glipizide + metformin (adjusted mean†) 0.1  
  95% Confidence Interval (-0.02, 0.2)‡  
Fasting Plasma Glucose (mg/dL) N=420 N=420
Baseline (mean) 162 161
Change from baseline (adjusted mean†) -9 -16
Difference from glipizide + metformin (adjusted mean†) 6  
  95% Confidence Interval (2, 11)§  
* Intent-to-treat population using last observation on study. 
† Least squares mean adjusted for baseline value.
‡ ONGLYZA + metformin is considered non-inferior to glipizide + metformin because the upper limit of this confidence interval is less than the prespecified non-inferiority margin of 0.35%.
§ Significance not tested.

 

Add-On Combination Therapy with Insulin (with or without metformin)

A total of 455 patients with type 2 diabetes participated in this 24-week, randomized, doubleblind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with insulin in patients with inadequate glycemic control (A1C ≥ 7.5% and ≤ 11%) on insulin alone (N=141) or on insulin in combination with a stable dose of metformin (N=314). Patients were required to be on a stable dose of insulin ( ≥ 30 units to ≤ 150 units daily) with ≤ 20% variation in total daily dose for ≥ 8 weeks prior to screening. Patients entered the trial on intermediate- or long-acting (basal) insulin or premixed insulin. Patients using short-acting insulins were excluded unless the short-acting insulin was administered as part of a premixed insulin.

Patients who met eligibility criteria were enrolled in a single-blind, four-week, dietary and exercise placebo lead-in period during which patients received insulin (and metformin if applicable) at their pretrial dose(s). Following the lead-in period, eligible patients were randomized to add-on therapy with either ONGLYZA 5 mg or placebo. Doses of the antidiabetic 33 therapies were to remain stable but patients were rescued and allowed to adjust the insulin regimen if specific glycemic goals were not met or if the investigator learned that the patient had self-increased the insulin dose by > 20%. Data after rescue were excluded from the primary efficacy analyses.

Add-on therapy with ONGLYZA 5 mg provided significant improvements from baseline to Week 24 in A1C and PPG compared with add-on placebo (Table 11). Similar mean reductions in A1C versus placebo were observed for patients using ONGLYZA 5 mg add-on to insulin alone and ONGLYZA 5 mg add-on to insulin in combination with metformin (-0.4% and -0.4%, respectively). The percentage of patients who discontinued for lack of glycemic control or who were rescued was 23% in the ONGLYZA group and 32% in the placebo group.

The mean daily insulin dose at baseline was 53 units in patients treated with ONGLYZA 5 mg and 55 units in patients treated with placebo. The mean change from baseline in daily dose of insulin was 2 units for the ONGLYZA 5 mg group and 5 units for the placebo group.

Table 11: Glycemic Parameters at Week 24 in a Placebo-Controlled Trial of ONGLYZA as Add-On Combination Therapy with Insulin*

EFFICACY PARAMETER ONGLYZA 5 MG + INSULIN (+/- METFORMIN)
N=304
PLACEBO + INSULIN (+/- METFORMIN) 
N=151
Hemoglobin A1C (%) N=300 N=149
Baseline (mean) 8.7 8.7
Change from baseline (adjusted mean†) -0.7 -0.3
Difference from placebo (adjusted mean†) −0.4‡  
  95% Confidence Interval (-0.6, -0.2)  
2-hour Postprandial Glucose (mg/dL) N=262 N=129
Baseline (mean) 251 255
Change from baseline (adjusted mean†) -27 -4
Difference from placebo (adjusted mean†) —23§  
  95% Confidence Interval (-37, -9)  
* Intent-to-treat population using last observation on study or last observation prior to insulin rescue therapy for patients needing rescue.
† Least squares mean adjusted for baseline value and metformin use at baseline.
‡ p-value < 0.0001 compared to placebo + insulin
§ p-value < 0.05 compared to placebo + insulin

 

The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C < 7% was 17% (52/300) with ONGLYZA in combination with insulin compared to 7% (10/149) with placebo. Significance was not tested.

Add-On Combination Therapy with Metformin plus Sulfonylurea

A total of 257 patients with type 2 diabetes participated in this 24-week, randomized, doubleblind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin plus a sulfonylurea in patients with inadequate glycemic control (A1C ≥ 7% and ≤ 10%). Patients were to be on a stable combined dose of metformin extended-release or immediate-release (at maximum tolerated dose, with minimum dose for enrollment being 1500 mg) and a sulfonylurea (at maximum tolerated dose, with minimum dose for enrollment being ≥ 50% of the maximum recommended dose) for ≥ 8 weeks prior to enrollment.

Patients who met eligibility criteria were entered in a 2-week enrollment period to allow assessment of inclusion/exclusion criteria. Following the 2-week enrollment period, eligible patients were randomized to either double-blind ONGLYZA (5 mg once daily) or double-blind matching placebo for 24 weeks. During the 24-week double-blind treatment period, patients were to receive metformin and a sulfonylurea at the same constant dose ascertained during enrollment. Sulfonylurea dose could be down titrated once in the case of a major hypoglycemic event or recurring minor hypoglycemic events. In the absence of hypoglycemia, titration (up or down) of study medication during the treatment period was prohibited.

ONGLYZA in combination with metformin plus a sulfonylurea provided significant improvements in A1C and PPG compared with placebo in combination with metformin plus a sulfonylurea (Table 12). The percentage of patients who discontinued for lack of glycemic control was 6% in the ONGLYZA group and 5% in the placebo group.

Table 12: Glycemic Parameters at Week 24 in a Placebo-Controlled Trial of ONGLYZA as Add-On Combination Therapy with Metformin plus Sulfonylurea*

EFFICACY PARAMETER ONGLYZA 5 MG + METFORMIN PLUS SULFONYLUREA 
N=129
PLACEBO + METFORMIN PLUS SULFONYLUREA 
N=128
Hemoglobin A1C (%) N=127 N=127
Baseline (mean) 8.4 8.2
Change from baseline (adjusted mean†) -0.7 -0.1
Difference from placebo (adjusted mean†) −0.7‡  
  95% Confidence Interval (-0.9, -0.5)  
2-hour Postprandial Glucose (mg/dL) N=115 N=113
Baseline (mean) 268 262
Change from baseline (adjusted mean†) -12 5
Difference from placebo (adjusted mean†) −17§  
  95% Confidence Interval (-32, -2)  
* Intent-to-treat population using last observation prior to discontinuation.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.0001 compared to placebo + metformin plus sulfonylurea
§ p-value < 0.05 compared to placebo + metformin plus sulfonylurea

 

The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C < 7% was 31% (39/127) with ONGLYZA in combination with metformin plus a sulfonylurea compared to 9% (12/127) with placebo. Significance was not tested.

Renal Impairment

A total of 170 patients participated in a 12-week, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of ONGLYZA 2.5 mg once daily compared with placebo in patients with type 2 diabetes and moderate (n=90) or severe (n=41) renal impairment or ESRD (n=39). In this trial, 98% of the patients were using background antidiabetic medications (75% were using insulin and 31% were using oral antidiabetic medications, mostly sulfonylureas).

After 12 weeks of treatment, ONGLYZA 2.5 mg provided significant improvement in A1C compared to placebo (Table 13). In the subgroup of patients with ESRD, ONGLYZA and placebo resulted in comparable reductions in A1C from baseline to Week 12. This finding is inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.

After 12 weeks of treatment, the mean change in FPG was -12 mg/dL with ONGLYZA 2.5 mg and -13 mg/dL with placebo. Compared to placebo, the mean change in FPG with ONGLYZA was -12 mg/dL in the subgroup of patients with moderate renal impairment, -4 mg/dL in the subgroup of patients with severe renal impairment, and +44 mg/dL in the subgroup of patients with ESRD. These findings are inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.

Table 13: A1C at Week 12 in a Placebo-Controlled Trial of ONGLYZA in Patients with Renal Impairment*

EFFICACY PARAMETER ONGLYZA 2.5 MG 
N=85
PLACEBO 
N=85
Hemoglobin A1C (%) N=81 N=83
Baseline (mean) 8.4 8.1
Change from baseline (adjusted mean†) -0.9 -0.4
Difference from placebo (adjusted mean†) −0.4‡  
95% Confidence Interval (-0.7, -0.1)  
* Intent-to-treat population using last observation on study.
† Least squares mean adjusted for baseline value.
‡ p-value < 0.01 compared to placebo

 

This monograph has been modified to include the generic and brand name in many instances.

 

Patient Information

ONGLYZA 
(on-GLY-zah) 
(saxagliptin) tablets

Read this Medication Guide carefully before you start taking ONGLYZA and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. If you have any questions about ONGLYZA, ask your healthcare provider.

What is the most important information I should know about ONGLYZA?

Serious side effects can happen to people taking ONGLYZA, including inflammation of the pancreas (pancreatitis) which may be severe and lead to death.

Certain medical problems make you more likely to get pancreatitis.

Before you start taking ONGLYZA:

Tell your healthcare provider if you have ever had

  • inflammation of your pancreas (pancreatitis)
  • stones in your gallbladder (gallstones)
  • a history of alcoholism
  • high blood triglyceride levels

It is not known if having these medical problems will make you more likely to get pancreatitis with ONGLYZA.

Stop taking ONGLYZA and contact your healthcare provider right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

What is ONGLYZA?

  • ONGLYZA is a prescription medicine used with diet and exercise to control high blood sugar (hyperglycemia) in adults with type 2 diabetes.
  • ONGLYZA lowers blood sugar by helping the body increase the level ofinsulin after meals.
  • ONGLYZA is unlikely by itself to cause your blood sugar to be lowered to a dangerous level (hypoglycemia) because it does not work well when your blood sugar is low. However, hypoglycemia may still occur with ONGLYZA. Your risk for getting hypoglycemia is higher if you take ONGLYZA with some other diabetes medicines, such as a sulfonylureaor insulin.
  • ONGLYZA is not for people with type 1 diabetes.
  • ONGLYZA is not for people with diabetic ketoacidosis (increased ketones in your blood or urine).
  • If you have had pancreatitis in the past, it is not known if you have a higher chance of getting pancreatitis while you take ONGLYZA.

It is not known if ONGLYZA is safe and effective in children younger than 18 years old.

Who should not take ONGLYZA?

Do not take ONGLYZA if you:

  • are allergic to any ingredients in ONGLYZA. See the end of this Medication Guide for a complete list of ingredients in ONGLYZA.

Symptoms of a serious allergic reaction to ONGLYZA may include:

  • swelling of your face, lips, throat, and other areas on your skin
  • difficulty with swallowing or breathing
  • raised, red areas on your skin (hives)
  • skin rash, itching, flaking, or peeling

If you have these symptoms, stop taking ONGLYZA and contact your healthcare provider right away.

What should I tell my healthcare provider before taking ONGLYZA?

Before you take ONGLYZA, tell your healthcare provider if you:

  • have kidney problems.
  • are pregnant or plan to become pregnant. It is not known if ONGLYZA will harm your unborn baby. If you are pregnant, talk with your healthcare provider about the best way to control your blood sugar while you are pregnant.
  • are breast-feeding or plan to breast-feed. ONGLYZA may be passed in your milk to your baby. Talk with your healthcare provider about the best way to feed your baby while you take ONGLYZA.

Tell your healthcare provider about all the medicines you take,including prescription and nonprescription medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

ONGLYZA may affect the way other medicines work, and other medicines may affect how ONGLYZA works. Contact your healthcare provider if you will be starting or stopping certain other types of medications, such as antibiotics, or medicines that treat fungus or HIV/AIDS, because your dose of ONGLYZA might need to be changed.

How should I take ONGLYZA?

  • Take ONGLYZA by mouth one time each day exactly as directed by your healthcare provider. Do not change your dose without talking to your healthcare provider.
  • ONGLYZA can be taken with or without food.
  • Do not split or cut ONGLYZA tablets.
  • During periods of stress on the body, such as:
    • fever
    • trauma
    • infection
    • surgery
      Contact your healthcare provider right away as your medication needs may change.
  • Your healthcare provider should test your blood to measure how well your kidneys are working before and during your treatment with ONGLYZA. You may need a lower dose of ONGLYZA if your kidneys are not working well.
  • Follow your healthcare provider's instructions for treating blood sugar that is too low (hypoglycemia). Talk to your healthcare provider if low blood sugar is a problem for you.
  • If you miss a dose of ONGLYZA, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take two doses at the same time unless your healthcare provider tells you to do so. Talk to your healthcare provider if you have questions about a missed dose.
  • If you take too much ONGLYZA, call your healthcare provider or Poison Control Center at 1-800-222-1222, or go to the nearest hospital emergency room right away.

What are the possible side effects of ONGLYZA?

ONGLYZA can cause serious side effects, including:

  • See “What is the most important information I should know about ONGLYZA?”
  • Allergic (hypersensitivity) reactions, such as:
    • swelling of your face, lips, throat, and other areas on your skin
    • difficulty with swallowing or breathing
    • raised, red areas on your skin (hives)
    • skin rash, itching, flaking, or peeling

If you have these symptoms, stop taking ONGLYZA and contact your healthcare provider right away.

Common side effects of ONGLYZA include:

  • upper respiratory tract infection
  • urinary tract infection
  • headache

Low blood sugar (hypoglycemia) may become worse in people who also take another medication to treat diabetes, such as sulfonylureas or insulin. Tell your healthcare provider if you take other diabetes medicines. If you have symptoms of low blood sugar, you should check your blood sugar and treat if low, then call your healthcare provider. Symptoms of low blood sugar include:

  • shaking
  • sweating
  • rapid heartbeat
  • change in vision
  • hunger
  • headache
  • change in mood

Swelling or fluid retention in your hands, feet, or ankles (peripheraledema) may become worse in people who also take a thiazolidinedione to treat diabetes. If you do not know whether you are already on this type of medication, ask your healthcare provider.

These are not all of the possible side effects of ONGLYZA. Tell your healthcare provider if you have any side effects that bother you or that do not go away. For more information, ask your healthcare provider.

Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How should I store ONGLYZA?

Store ONGLYZA between 68°F and 77°F (20°C and 25°C).

Keep ONGLYZA and all medicines out of the reach of children.

General information about the use of ONGLYZA

Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use ONGLYZA for a condition for which it was not prescribed. Do not give ONGLYZA to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about ONGLYZA. If you would like to know more information about ONGLYZA, talk with your healthcare provider. You can ask your healthcare provider for additional information about ONGLYZA that is written for healthcare professionals. For more information, go to www.ONGLYZA.com or call 1-800-ONGLYZA.

What are the ingredients of ONGLYZA?

Active ingredient: saxagliptin

Inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, and iron oxides.

What is type 2 diabetes?

Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that your body produces does not work as well as it should. Your body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems.

The main goal of treating diabetes is to lower your blood sugar so that it is as close to normal as possible.

High blood sugar can be lowered by diet and exercise, and by certain medicines when necessary.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

SAXAGLIPTIN - ORAL

 

(SAX-a-GLIP-tin)

 

COMMON BRAND NAME(S): Onglyza

 

USES: Saxagliptin is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used by people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

Saxagliptin works by increasing levels of natural substances called incretins. Incretins help to control blood sugar by increasing insulin release, especially after a meal. They also decrease the amount of sugar your liver makes.

 

HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using saxagliptin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually once daily.

The manufacturer directs not to split/cut the tablet before taking it. However, many similar drugs (immediate-release tablets) can be split/cut. Follow your doctor's directions on how to take this medication.

The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Carefully follow the medication treatment plan, meal plan, and exercise program your doctor has recommended.

 

 

 

Consumer Overview Side Effect

SIDE EFFECTS: Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Although saxagliptin by itself usually does not cause low blood sugar (hypoglycemia), low blood sugar may occur if this drug is prescribed with other anti-diabetic medications. Talk with your doctor or pharmacist about all your diabetic medication(s).

Symptoms of low blood sugar include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you don't have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda. Tell your doctor immediately about the reaction and the use of this product. Low blood sugar is more likely if you drink large amounts of alcohol, do unusually heavy exercise, or do not consume enough calories from food. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Talk with your doctor or pharmacist about what to do if you miss a meal.

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor immediately. Your dosage may need to be increased.

Stop taking saxagliptin and get medical help right away if this very serious side effect occurs: signs of disease of the pancreas (such as severe stomach/abdominal pain which may spread to the back, persistent nausea/vomiting).

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Onglyza (saxagliptin tablets) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking saxagliptin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, disease of the pancreas (pancreatitis), risk factors for pancreatitis (such as stones in your gallbladder, regular use/abuse of alcohol, high levels of fats/triglycerides in the blood).

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely.

Limit alcohol while taking this medication because it can increase your risk of developing low blood sugar and pancreatitis.

It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Pregnancy may cause or worsen diabetes. Discuss a plan with your doctor for managing your blood sugar while pregnant. Your doctor may change your diabetes treatment during your pregnancy (such as diet and medications including insulin).

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

 

 

 

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Beta-blocker medications (such as metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of low blood sugar, such as dizziness, hunger, or sweating, are unaffected by these drugs.

Many drugs can affect your blood sugar levels, making it more difficult to control your blood sugar. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor about the results and of any symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your anti-diabetic medication, exercise program, or diet.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Attend a diabetes education program to learn more about diabetes and the important aspects of its treatment, including medications, diet, exercise, and getting regular eye/foot/medical exams. Learn the symptoms of high and low blood sugar and how to treat low blood sugar. Check your blood sugar levels regularly as directed.

Keep all regular medical and laboratory appointments. Laboratory tests (such as kidney function tests, fasting blood glucose, hemoglobin A1c) should be performed periodically to monitor your progress or check for side effects.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised March 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Onglyza

Generic Name: saxagliptin (Pronunciation: SAX a GLIP tin)

  • What is saxagliptin (Onglyza)?
  • What are the possible side effects of saxagliptin (Onglyza)?
  • What is the most important information I should know about saxagliptin (Onglyza)?
  • What should I discuss with my healthcare provider before taking saxagliptin (Onglyza)?
  • How should I take saxagliptin (Onglyza)?
  • What happens if I miss a dose (Onglyza)?
  • What happens if I overdose (Onglyza)?
  • What should I avoid while taking saxagliptin (Onglyza)?
  • What other drugs will affect saxagliptin (Onglyza)?
  • Where can I get more information?

What is saxagliptin (Onglyza)?

 

Saxagliptin is an oral diabetes medicine that helps control blood sugar levels. It works by regulating the levels of insulin your body produces after eating.

Saxagliptin is for people with type 2 diabetes. Saxagliptin is sometimes used in combination with other diabetes medications, but is not for treating type 1 diabetes.

Saxagliptin may also be used for purposes not listed in this medication guide.

Onglyza 2.5 mg

round, yellow, imprinted with 2.5, 4214

What are the possible side effects of saxagliptin (Onglyza)?

 

Get emergency medical help if you have any of thesesigns of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
  • pain or burning when you urinate;
  • swelling in your hands, ankles, or feet; or
  • easy bruising or bleeding.

Less serious side effects may include:

  • runny or stuffy nose, sore throat, cough;
  • headache; or
  • stomach pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Onglyza (saxagliptin tablets) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about saxagliptin (Onglyza)?

 

Do not use this medication if you are allergic to saxagliptin or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

Before you take saxagliptin, tell your doctor if you have kidney disease or if you are on dialysis.

You may take this medicine with or without food. Follow your doctor's instructions.

Saxagliptin is only part of a complete program of treatment that also includes diet, exercise, weight control, and possibly other medications. It is important to use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Side Effects Centers
  • Onglyza

Patient Detailed How Take

What should I discuss with my healthcare provider before taking saxagliptin (Onglyza)?

 

Do not use this medication if you are allergic to saxagliptin, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

To make sure you can safely take saxagliptin, tell your doctor if you have kidney disease or if you are on dialysis.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether saxagliptin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Saxagliptin should not be given to a child younger than 18 years old without a doctor's advice.

How should I take saxagliptin (Onglyza)?

 

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

You may take this medicine with or without food. Follow your doctor's instructions.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.

Your doctor may want you to stop taking saxagliptin for a short time if you become ill, have a fever or infection, or if you have surgery or a medical emergency.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office. Visit your doctor regularly.

Saxagliptin is only part of a complete program of treatment that also includes diet, exercise, weight control, and possibly other medications. It is important to use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat

Side Effects Centers
  • Onglyza

Patient Detailed Avoid Taking

What happens if I miss a dose (Onglyza)?

 

Take the missed dose as soon as you remember (be sure to take the medicine with food if your doctor has instructed you to). Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Onglyza)?

 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You may have signs of low blood sugar, such as extreme weakness, confusion, tremors, sweating, fast heart rate, trouble speaking, nausea, vomiting, rapid breathing, fainting, and seizure (convulsions).

What should I avoid while taking saxagliptin (Onglyza)?

 

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect saxagliptin (Onglyza)?

 

Tell your doctor about all other medications you use, especially:

  • conivaptan (Vaprisol);
  • diclofenac (Arthrotec, Cataflam, Voltaren, Flector Patch, Solareze);
  • imatinib (Gleevec);
  • isoniazid (for treating tuberculosis);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), or telithromycin (Ketek);
  • an antidepressant such as nefazodone;
  • antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);
  • heart or blood pressure medication such as nicardipine (Cardene) or quinidine (Quin-G);
  • HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir, Kaletra); or
  • insulin or an oral diabetes medication such as glipizide (Glucotrol, Metaglip), glimepiride (Amaryl, Avandaryl, Duetact), glyburide (DiaBeta, Micronase, Glucovance), and others.

This list is not complete and other drugs may interact with saxagliptin. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about saxagliptin.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 5.01. Revision date: 12/30/2011.

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